Project Summary The goal of this project is to investigate and quantify the direct and mediated associations between major depressive disorder, clinically significant depressive symptoms, and falls, using data from a large, nationally- representative longitudinal cohort study of older adults in the US. Falls often lead to injury, disability, substantial health service costs and are the leading cause of injury-related mortality in adults age 65 and older. Risk for and recovery from falls is determined by several factors including environmental hazards, physiological vulnerability, cognition, medications, mental health, and social support. While extensive research literature describes the role of environment and physiology in fall risk, little is known about the role of mental health. Evidence suggests that individuals with major depressive disorder (the most common mental health disorder among older adults) may be up to four times as likely to experience an unintentional fall and more likely to experience injury because of a fall than their non-depressed counterparts. Several correlates of depression have been implicated as potential mediators or moderators of this association, such as antidepressant medication use, cognitive impairment, frailty, and diminished social networks, but the relative importance of these mechanisms is unknown. This project will address this important gap in knowledge by identifying and quantifying key mechanistic pathways between depression and falls, using a novel causal mediation analytic approach. This study will use longitudinal data from the nationally-representative Health and Retirement Study spanning from 2006 to 2010 to address the following specific aims: Aims 1 & 2: Determine the relative and absolute extent to which the associations between major depressive disorder, clinically significant depressive symptoms and fall risk are mediated by frailty, cognitive impairment, and antidepressant medications. Aim 3: To estimate the direct and serially mediated effects of depression on functional abilities (instrumental activities of daily living and activities of daily living) through falls. By providing evidence of the relative and absolute risk of falls associated with depression, this study will provide key information at two complementary levels. First, describing the relative influence of different fall mechanisms will inform the development of comprehensive strategies to treat depression in older adults with vulnerability to falls and fall-related injuries. Second, by providing quantitative evidence of different paths from depression to falls and fall-related functional impairment, this project will inform the development and prioritization of policies and strategies aimed at fall prevention for older adults in general.